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Biomedical subjects

A Joseph

Publications and source records attributed to A Joseph.

At least 19 recordsLinked to original sources
PubMed2006

Syphilitic acute posterior placoid chorioretinitis in nonimmuno-compromised patients.

PURPOSE: To describe the clinical and angiographic features of three cases of secondary syphilis in immunocompetent patients, which presented as acute posterior placoid chorioretinitis (APPC) to the ophthalmologist. METHODS: Interventional case series. The aetiology of the APPC was confirmed by serology to be secondary syphilis. Optical coherence tomography, electrophysiology, fundus fluorescein, and indocyanine green (ICG) angiography were performed at presentation and after resolution. Appropriate treatment for secondary syphilis was instituted in each patient. RESULTS: The clinical features, fundus fluorescein and ICG angiography, multifocal electroretinography (mfERG), and optical coherence tomography findings of APPC are described. All three patients had a satisfactory resolution of the APPC with improvement in visual acuity. CONCLUSIONS: APPC in secondary syphilis can occur even in immunocompetent patients. A high index of suspicion is required for early diagnosis of this condition resulting in a good visual outcome with adequate treatment. mfERG and optical coherence tomography are useful in the diagnosis and follow-up of these patients.

Adult↗
PubMed2006

Tacrolimus immunosuppression in high-risk corneal grafts.

BACKGROUND: Unlike the immune privilege enjoyed by low-risk corneal grafts, high-risk corneal grafts experience rejection rates comparable to liver and kidney transplants. Systemic immunosuppression reduces the risk of rejection in high-risk corneal grafts. METHODS: Systemic tacrolimus, a specific T cell inhibitor, was used at a mean daily dose of 2.5 mg to immunosuppress 43 patients undergoing high-risk corneal transplantation. Immunosuppression was continued for a period of 18-24 months after the high-risk corneal graft. RESULTS: During a mean follow-up period of 33.7 months, clarity of the graft was maintained in 65% of patients. Eight patients experienced rejection episodes while on tacrolimus, and this led to graft failure in five patients. CONCLUSION: Tacrolimus is relatively safe and effective in reducing rejection and prolonging graft survival in patients with high-risk keratoplasty compared with other series where similar immunosuppression was not used.

Administration, Oral↗
PubMed2006

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.

Child, Preschool↗
PubMed2006

Epithelial proliferative potential of organ cultured corneoscleral rims; implications for allo-limbal transplantation and eye banking.

AIMS: To determine the epithelial proliferative capacity of organ cultured limbal tissue and correlate this with various donor and eye banking factors. METHODS: 24 corneoscleral limbal (CSL) rims left over from penetrating keratoplasty were split in half and set up as in vitro explant cultures. Corneal epithelial proliferative potential (CEPP) was assessed by the number of "cycles" of growth achieved before explants underwent exhaustion and failure to generate an epithelium to subconfluence. The dependence of CEPP on the age of the donor, time of death to enucleation, time of enucleation to organ culture, and time in organ culture in the eye bank was determined. RESULTS: CSL rims were capable of up to four cycles of culture with a wide variation between tissue samples. Of the various factors examined, death to enucleation time was the only statistically significant factor affecting the CEPP (regression coefficient: -0.062 (cycles/hour), CI -0.119 to -0.004, p = 0.037). Time in organ culture had little effect on CEPP. CONCLUSIONS: Preselected organ cultured CSL rims from eye banks may offer a viable alternative tissue source for use in allo-limbal transplantation.

Adult↗
PubMed2006

Rates and factors associated with suicide in Kaniyambadi Block, Tamil Nadu, South India, 2000-2002.

BACKGROUND: Inefficient civil registration systems, non-report of deaths, variable standards in certifying death and the legal and social consequences of suicide are major obstacles to investigating suicide in the developing world. OBJECTIVE: The aim of this study was to prospectively determine the suicide rate in Kaniyambadi Block, Tamil Nadu, South India, for the years 2000-2002 using verbal autopsies. METHOD: The setting for the study was a comprehensive community health programme in a development block in rural South India. The main outcome measure was death by suicide, diagnosed by a detailed verbal autopsy and census, and birth and death data to identify the population base. RESULTS: The average suicide rate was 92.1 per 100,000. The ratio of male to female suicides was 1:0.66. The age-specific suicide rate for men increased with age while that for women showed two peaks: 15-24 years and over 65 years of age. Hanging (49%) and poisoning with organo-phosphorus compounds (40.5%) were the commonest methods of committing suicide. Acute and/or chronic stress was elicited for nearly all subjects. More men suffered from chronic stress while more women had acute precipitating events (chi2 = 4.58; p < 0.04). People less than 44 years of age had more acute precipitating events before death while older subjects reported more chronic stress (chi2 = 17.38; p < 0.001). CONCLUSION: The study replicates findings of an earlier study from the area. The suicide rate documented in this study is very high and is a major public health concern. There is a need for sentinel centres in India and in developing countries to monitor trends and to develop innovative strategies to reduce deaths by suicide.

Adolescent↗
PubMed2005

Novel dextran-spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers.

Recently, a novel cationic polymer, dextran-spermine (D-SPM) was developed for gene delivery. An efficient transfection was obtained using this polycation for a variety of genes and cell lines in serum-free or serum-poor medium. However, transfection using the water-soluble D-SPM-based polyplexes decreased with increasing serum concentration in cell culture in a concentration-dependent manner, reaching 95% inhibition at 50% serum in the cell growth medium. In order to overcome this obstacle, oleyl derivatives of D-SPM (which form micelles in aqueous phase) were synthesized at 1, 10, and 20 mol% of oleyl moiety to polymer epsilon-NH2 to form N-oleyl-D-SPM (ODS). Polyplexes based on ODS transfected well in medium containing 50% serum. Comparison with polyplexes based on well-established polymers (branched and linear polyethyleneimine) and with DOTAP/Cholesterol lipoplexes showed that regarding beta-galactosidase transgene expression level and cytotoxicity in tissue culture, the D-SPM and ODS compare well with the above polyplexes and lipoplexes. Intracellular trafficking using FITC-labeled ODS and Rhodamine-labeled pGeneGrip plasmid cloned with hBMP2 monitored by confocal microscopy revealed that during the transfection process the fluorescent-labeled polymer concentrates in the Golgi apparatus and around the nucleus, while the cell cytoplasm was free of fluorescent particles, suggesting that the polyplexes move in the cell toward the nucleus by vesicular transport through the cytoplasm and not by a random diffusion. We found that the plasmids penetrate the cell nucleus without the polymer. Preliminary results in zebra fish and mice demonstrate the potential of ODS to serve as an efficient nonviral vector for in vivo transfection.

Animals↗
PubMed2005

Induction and differential expression of beta-1,3-glucanase mRNAs in tolerant and susceptible Hevea clones in response to infection by Phytophthora meadii.

Most cultivated rubber tree (Hevea brasiliensis Willd. ex A. Juss.) clones in India are susceptible to abnormal leaf fall disease (ALF), which is caused by various Phytophthora species and results in yield losses of up to 40%. Because the conventional breeding programs for this perennial tree crop are complex and time consuming, we attempted to find a molecular solution to increase the tolerance of rubber trees to ALF. The expression patterns of the gene coding for the pathogenesis-related beta-1,3-glucanase (beta-glu) enzyme in a tolerant (RRII 105) and a highly susceptible (RRIM 600) clone of rubber tree were examined, following infection with ALF-causing Phytophthora meadii McRae. Infected leaf samples were collected at different times after inoculation, and RNA was extracted and subjected to Northern blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). On hybridization with a 1.25 kb beta-glu probe, Northern blots showed a marked increase in beta-glu transcript levels in both clones 48 h after inoculation. However, compared with the susceptible RRIM 600 clone, the tolerant RRII 105 clone had a higher rate of increase and a more prolonged induction, with beta-glu transcript levels remaining high for 4 days after inoculation. In RRIM 600, the mRNA levels decreased significantly 48 h after inoculation. On re-hybridization with an 18S rRNA probe, uniform signals were detected in all the lanes, indicating that an equal amount of total RNA was present in all samples. Similar results were obtained in relative quantitative RT-PCR experiments with the housekeeping actin gene as an internal control. Thus, although induction of the beta-glu gene occurred in both tolerant and susceptible clones, the predominant difference between clones was in the intensity and duration of the response. The tolerance of clone RRII 105 may be associated with the prolonged expression of the gene following infection. The antifungal activity of these hydrolase enzymes makes them rational candidates for overexpression by genetic transformation to produce disease resistant crops.

Enzyme Induction↗
PubMed2005

The efficacy of sirolimus in the treatment of patients with refractory uveitis.

AIMS: To determine the efficacy of sirolimus in the treatment of patients with severe non-infectious uveitis. METHODS: Eight patients with severe non-infectious uveitis were recruited to an open study. Inclusion criteria were limited to patients whose disease was not controlled with at least two or more separate steroid sparing immunosuppressants (either because of unacceptable side effects or ineffectiveness of the drug) or who required regular doses of corticosteroids either as high dose systemic or orbital floor injections in order to control their disease. Intraocular inflammation, visual acuity, symptoms, corticosteroid burden, drug toxicity, and side effects were monitored. RESULTS: Sirolimus therapy was effective in five of the eight patients, all of whom had their dose of corticosteroids reduced or discontinued. Treatment in three patients was considered a failure as it caused intolerable side effects and/or failed to control the uveitis. Side effects were common and were typically gastrointestinal or cutaneous in nature. The severity of symptoms was dose dependent in most cases and occurred at trough blood levels above 25 ng/ml. CONCLUSION: Sirolimus is an effective and potent immunosuppressive treatment in the majority of patients with non-infectious uveitis and can reduce the need for long term supplementary corticosteroid therapy. Further studies are required to establish the long term efficacy and safety of sirolimus alone or in combination with other steroid sparing immunosuppressants.

Adult↗
PubMed2005

Limbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche.

BACKGROUND/AIMS: There is substantial evidence that mammalian epithelial stem cells are located within well defined niches. Although the corneoscleral limbus is acknowledged as the site of corneal epithelial stem cells no anatomical niche for such cells has yet been described. The authors undertook to re-evaluate the microanatomy of the limbus in order to identify possible sites that may represent a stem cell niche. METHODS: Systematic serial 5-7 microm sections of human corneoscleral segments obtained from cadaver donors, were examined. The sections were stained with haematoxylin and eosin or toludine blue. Sections with specific areas of interest were further examined immunohistologically for the corneal epithelial marker cytokeratin 14 and the "stem cell" marker ABCG2 transporter protein. RESULTS: Distinct anatomical extensions from the peripheral aspect of the limbal palisades were identified. These consist of a solid cord of cells extending peripherally or circumferentially. The cells stained positive for CK14 and ABCG2. CONCLUSIONS: A novel anatomical structure has been identified at the human limbus, which demonstrates characteristics of being a stem cell niche. The authors have termed this structure the limbal epithelial crypt.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

Impression cytology of the ocular surface.

Impression cytology refers to the application of a cellulose acetate filter to the ocular surface to remove the superficial layers of the ocular surface epithelium. These cells can then be subjected to histological, immunohistological, or molecular analysis. Proper technique is essential as the number of cells sampled can vary considerably. Generally two to three layers of cells are removed in one application but deeper cells can be accessed by repeat application over the same site. Applications for impression cytology include diagnosing a wide range of ocular surface disorders, documenting sequential changes in the conjunctival and corneal surface over time, staging conjunctival squamous metaplasia, and monitoring effects of treatment. It is also a useful investigational tool for analysing ocular surface disease with immunostaining and DNA analysis. It is non-invasive, relatively easy to perform, and yields reliable information about the area sampled with minimal discomfort to the patient. Major ophthalmic centres should develop and introduce this technique into routine clinical practice. This is best achieved with a team approach including the ophthalmologist, pathologist, microbiologist, and the immunologist.

Conjunctiva↗
PubMed2005

Laparoscopic colorectal surgery: learning curve and training implications.

AIMS: This paper is a review of experience of laparoscopic colorectal surgery at a district general hospital with particular emphasis on the learning curve and training implications. METHODS: All patients undergoing colorectal surgery where laparoscopy was attempted between March 1998 and October 2003 were included in this study. RESULTS: There were 80 patients of which 49 had malignancy. Twenty eight stomas and 52 bowel resections were performed laparoscopically. The conversion rate for bowel resection was 32% (decreasing from 38% to 44% to 22%). This was significant (p = 0.001) when compared with stoma formation (7%). The firm has support from a specialist registrar and staff grade surgeon. In 22% of cases, one of the middle grades was the principal operating surgeon, mainly laparoscopic mobilisation and stoma formation. Only 6% of resections were performed by the middle grades. Conversely, a middle grade was the main operating surgeon in 66% of open resections and 61% of stoma formations during the same period. There were in all two deaths and 14 postoperative complications. All patients who had laparoscopic resections for malignancy had clear resection margins. CONCLUSION: This audit highlights that there is a long learning curve in laparoscopic colorectal surgery with decrease in conversion rates with increasing experience. There is also a reduction in training opportunities in open surgery during the learning phase of the consultant, although this may be counterbalanced by the exposure to laparoscopic techniques. Laparoscopic colonic mobilisation, as a part of stoma formation, is a good starting point for specialist registrar training.

Adult↗
PubMed2004

Maternal depression and low maternal intelligence as risk factors for malnutrition in children: a community based case-control study from South India.

AIMS: To determine whether current and postpartum maternal depression and low maternal intelligence are risk factors for malnutrition in children. METHODS: In rural South India 72 children with malnutrition were identified from a central register; 72 controls were matched for age, gender, and residence. RESULTS: Major depression in the postpartum period (OR 5.0, 95% CI 1.0 to 24.0), current major depression (OR 3.2, 95% CI 1.1 to 9.5), and low maternal intelligence (OR 3.8, 95% CI 1.3 to 11.1) were associated with malnutrition in the child. Low birth weight (OR 2.9, 95% CI 1.2 to 6.8) was also significantly associated with infant malnutrition. Conditional logistic regression adjusting for all other determinants yielded the following results: major depression during the postpartum period (OR 7.8; 95% CI 1.6 to 38.51), current major depression (OR 3.1; 95% CI 0.9 to 9.7), low maternal intelligence (OR 4.6; 95% CI 1.5 to 14.1), and low birth weight (OR 2.7; 95% CI 2.5 to 6.8). The interactions between current maternal depression and low birth weight and between postpartum depression and low maternal intelligence were statistically significant. The level of maternal intelligence was associated with nutritional status. The severity of malnutrition was also significantly associated with major depression during the postpartum period and low maternal intelligence. CONCLUSION: There is evidence for an association between postpartum maternal depression, low maternal intelligence, and low birth weight with malnutrition in children aged 6-12 months.

Adult↗
PubMed2004

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes.

BACKGROUND/AIMS: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. METHODS: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. RESULTS: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). CONCLUSION: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes.

Antigens, CD↗
PubMed2004

Epithelial cell characteristics of cultured human limbal explants.

AIM: To determine the immunohistochemical characteristics of putative corneal epithelial stem cells remaining on limbal explants maintained in culture. METHODS: Human limbal explant cultures were generated from 25 residual corneoscleral donor rims following penetrating keratoplasty. Serial sections of these explants were studied using immunohistochemical techniques with a panel of antibodies, on day 0 and 1, 2, and 3 weeks. RESULTS: The number of epithelial cells expressing cytokeratin 19 and vimentin increased with duration in culture, while the number of cells expressing cytokeratin 3 decreased. Connexin 43 expression was lost by 1 week in culture. p63 was expressed by cells that had migrated around the explant and the number of p63 positive cells decreased with longer duration in culture. The explants were initially negative for Ki67, but the epithelial cells were positive at 1 week, and expression of Ki67 was progressively lost with increasing duration in culture. The initial uniform staining of the epithelium for epidermal growth factor receptor and alpha enolase remained unchanged at 3 weeks. CONCLUSIONS: There is an expansion of less differentiated (cytokeratin 3 negative and CK19/vimentin positive) epithelial cells on corneoscleral explants maintained in culture for 3 weeks. The pattern of expression of p63 noted in this study does not support the suggestion that it is a marker of limbal stem cells. The decline in p63 and Ki67 expression among the epithelial cells of the cultured explant button implies that as the epithelial sheet outgrowing from the explant button reaches confluence, the proliferative status of the cells remaining on the explant button declines. These findings are of clinical relevance as explants of limbal tissue are used in limbal stem cell transplantation. There is no information available to date on the fate of epithelial cells on such explants. This study provides some insight into this and suggests that an expansion of the stem cell pool or its progeny may occur in limbal explants.

Cell Division↗
PubMed2004

The efficacies of affected-limb care with penicillin diethylcarbamazine, the combination of both drugs or antibiotic ointment, in the prevention of acute adenolymphangitis during bancroftian filariasis.

Repeated attacks of adenolymphangitis (ADL) contribute significantly to the progression of chronic lymphoedema in lymphatic filariasis. They are a cause of stigma and, since they may prevent work and require treatment for which payment must be made, of economic loss. The aim of the present study was to improve the treatment of ADL attacks, which is currently mostly empirical. In a double-blind, placebo-controlled, clinical study, 150 subjects who had each suffered at least two ADL attacks in the preceding year were enrolled and randomly allocated to a programme of self-care of the affected limb (after an intensive training programme) and one of five treatments for 12 months. The subjects were supplied with tablets and ointment so that they could take oral penicillin (800 mg/day), oral diethylcarbamazine (DEC; 1 mg/kg.day) or both of these drugs (at the same doses), or apply framycetin ointment to the affected limb, or just take placebo tablets and apply placebo (zinc-oxide) ointment. Placebo tablets and placebo ointment were used so that neither the subjects nor those assessing the responses to treatment were aware of the treatment arm to which each subject had been assigned. The subjects were requested to continue with the affected-limb care after they had stopped taking the tablets and applying the cream, and were followed-up for 24 months from the first treatment.Overall, the mean incidence of ADL attacks decreased from 2.7 episodes/person-year in the pre-treatment year to just 0.38 episode/person-year during the treatment year (P< 0.01). The greatest reduction in incidence was seen in the 58 subjects who received penicillin (with or without DEC). Even in the placebo group, however, the incidence of ADL in the treatment year was significantly lower than that seen in the pre-treatment year, indicating that affected-limb care on its own helps to prevent some attacks. In all groups except the placebo, the incidence of ADL attacks in the year post-treatment exceeded that seen in the treatment year, indicating that chemoprophylaxis needs to be continued for more than a year if such attacks are to be prevented. In most (84%) of the attacks recorded, titres of anti-streptococcal antibodies were seen to be elevated (compared with those recorded during convalescence),indicating that streptococci have a role in the aetiology of ADL. It is recommended that a combination of penicillin prophylaxis and affected-limb care be incorporated into filariasis-control programmes, to decrease morbidity.

Acute Disease↗